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A gH/gL-encoding replicon vaccine elicits neutralizing antibodies that protect humanized mice against EBV challenge.

Kristina R EdwardsHarman MalhiKarina SchmidtAmelia R DavisLeah J HomadNikole L WarnerCrystal B ChhanSamuel C ScharffenbergerKaren GaffneyTroy C HinkleyNicole B PotchenJing Yang WangJason PriceM Juliana McElrathJames OlsonNeil P KingJennifer M LundZoe MoodieJesse H ErasmusAndrew T McGuire
Published in: NPJ vaccines (2024)
Epstein-Barr virus (EBV) is associated with several malignancies, neurodegenerative disorders and is the causative agent of infectious mononucleosis. A vaccine that prevents EBV-driven morbidity and mortality remains an unmet need. EBV is orally transmitted, infecting both B cells and epithelial cells. Several virally encoded proteins are involved in entry. The gH/gL glycoprotein complex is essential for infectivity irrespective of cell type, while gp42 is essential for infection of B cells. gp350 promotes viral attachment by binding to CD21 or CD35 and is the most abundant glycoprotein on the virion. gH/gL, gp42 and gp350, are known targets of neutralizing antibodies and therefore relevant immunogens for vaccine development. Here, we developed and optimized the delivery of several alphavirus-derived replicon RNA (repRNA) vaccine candidates encoding gH/gL, gH/gL/gp42 or gp350 delivered by a cationic nanocarrier termed LION™. The lead candidate, encoding full-length gH/gL, elicited high titers of neutralizing antibodies that persisted for at least 8 months and a vaccine-specific CD8 + T cell response. Transfer of vaccine-elicited IgG protected humanized mice from EBV-driven tumor formation and death following high-dose viral challenge. These data demonstrate that LION/repRNA-gH/gL is an ideal candidate vaccine for preventing EBV infection and/or related malignancies in humans.
Keyphrases
  • epstein barr virus
  • diffuse large b cell lymphoma
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  • high dose
  • sars cov
  • low dose
  • drug delivery
  • metabolic syndrome
  • electronic health record
  • high fat diet induced
  • big data
  • monoclonal antibody